Mounting evidence shows that functional connections between the cellular building blocks within the brain actively reorganize, even in the mature brain. Even so, this view is not yet universally accepted in part because tracking these changes in the awake, behaving animal is technically challenging. Further complicating the question of changes in single neuron properties with experience is the fact that cortex comprises many cell types, and recent data from the applicant's laboratory has revealed that plasticity may be expressed differentially across these populations. This proposal focuses on vision as a powerful model system for exploring the role that plasticity plays in normal brain function. The general hypothesis to be tested is that effective visual processing relies on experience driven, adaptive firing patterns of neurons within the inferior temporal cortex (IT), and that this experience leads to differential physiological changes in excitatory and inhibitory neurons. These changes, in turn, support measurable behavioral advantages. Although changes in neural responses are typically slow, artificial control of neural activity can induce modification more rapidly, and this modified activity can guide visually directed behavior. The proposed experiments will support efforts aimed at reviving or augmenting adaptive responses in higher-level visual areas. The proposal has three fundamental aims. The first aim is to clearly demonstrate impact of long-term familiarity on visual processing for multiple object classes. The strategy for accomplishing this aim will be to track performance in a speeded recognition tasks with well-known and trial unique stimuli. The second aim is to determine how visual experience affects stimulus encoding by neurons in anterior IT cortex. This will be achieved by tracking single neuron and small population activity by combining recording of activity across spatial scales and using carefully generated visual stimuli during the tasks developed in the first aim. The final aim is to directly manipulate neuron activity in temporal cortex to control plasticity. This aim will leverage optogenetic stimulation methods already in use in the applicant's laboratory to affect neural responses on single trials in order to induce the kinds of plasticity observed in the second aim. Together, the results of this work will help bridge the large literature on synaptic plasticity at he cellular level with visual behavior in primates. An important specific focus of these studies will e to identify stimulus, task, and physiological conditions under which both excitatory and inhibitory neurons adapt their responses through long-term experience, and to show how this plasticity can positively influence behavior. That visual experience can profoundly alter visual object representations in IT is of critical importance to efforts directed at repair of the visual system nd in understanding development disorders. Using an innovative set of tools and approaches, the projects in this proposal will emphasize the need to carefully track cellular activity in behaving animals, using complex and demanding real world tasks, with a level of resolution that will likely prove essential for future studies, and models, of higher brain function.